The goal of the proposed research is to determine if serial assessment of novel risk factors for cardiovascular disease (CVD) is an important tool in prediction of clinical CVD events in an elderly cohort, the Cardiovascular Health Study. The researchers have exciting new data showing strong associations of biomarkers of hemostasis and inflammation with increased CVD risk in apparently healthy subjects over 65. These unique results, along with results of the proposed research, may have a major impact on practice of cardiovascular medicine. To define normal longitudinal change, the biomarkers of interest will be measured at two time points three years apart. A nested case-control study with myocardial infarction and CVD death as endpoints, will be completed to study the relationship between longitudinal change of biomarkers and CVD risk. Effect modification by subclinical CVD will be assessed. Levels of biomarkers at the two time points will be used to determine whether proximity of measurement to CVD event is an important determinant of predictive utility of the markers. Prediction models will be developed and validated to identify older individuals at the highest risk of future CVD. The candidate is committed to becoming an independent investigator in cardiovascular epidemiology. Along with her excellent medical background, to accomplish her goal, expertise is required in epidemiology, biostatistics, and molecular biochemistry and physiology. The candidate has begun training in all three areas, pursuing a masters degree in Epidemiology, studying the epidemiology of hemostasis in the elderly, and participating in research with a notable biochemistry group. The goal of this award is to support expanded knowledge and solidification of all three key areas of molecular epidemiology, through an important research project. This will facilitate success of the candidate in molecular cardiovascular epidemiology. The environment for the proposed research is ideal for the candidate's needs. The sponsor, RP Tracy, a clinical chemist, has a significant role as a molecular epidemiologist, having built a large laboratory with a reputation for high-precision biomarker assessment in many epidemiologic studies. He is committed to the candidate, as demonstrated in the application. The cosponsor, LH Kuller, has contributed broadly to the field of cardiovascular epidemiology, and supplements the skills of Dr. Tracy. The expertise of the other advisors is diverse and well matched to the career development plans of the candidate, and to the aims of the research. A critical factor to the success of the applicant is the unequivocal commitment of the institution to her career development.